Table 6.

Nail psoriasis studies

Study	Design	Therapy	Dosage	Sample size	Patient demographics (age/sex)	Nail involvement	Outcomes
Scher et al. (2001) [62]	Randomized, double-blind, controlled trial	Topical tazarotene	Vehicle gel; tazarotene 0.1% gel nightly to 2 target nails, one nail occluded, one nail not occluded	31 patients	Mean age 43 years; 9 female patients and 22 male patients	Fingernails	Compared to vehicle gel, tazarotene resulted in significantly greater reduction in onycholysis in occluded nails (p ≤ 0.05 at weeks 4 and 12) and a significantly greater reduction in onycholysis in nonoccluded nails (p ≤ 0.05 at week 24). The tazarotene treatment arm also had significantly greater decrease in nail pitting in occluded nails (p ≤ 0.05 at week 24). There was no difference between treatment arms for subungual hyperkeratosis, leukonychia, nail plate crumbling, splinter hemorrhage, and nail growth rate. 5/21 tazarotene gel patients reported adverse events, including proximal nail fold skin peeling, skin irritation, periungual irritation, paronychia, and proximal nail fold erythema.
Rigopoulos et al. (2007) [63]	Randomized, double-blind trial	Topical tazarotene	Tazarotene 0.1% cream occluded nightly; clobetasol propionate 0.05% cream	46 patients	Age NR; sex NR	Fingernails and toenails	Both treatment arms showed improvement in pitting, onycholysis, hyperkeratosis, and salmon patches (p < 0.001) after 12 weeks of therapy. There was no statistically significant difference in improvement between treatment arms at 12 weeks. At 24 weeks, tazarotene treatment had a greater reduction in hyperkeratosis (p < 0.001). Adverse events were reported in 3/16 (18.75%) patients in the tazarotene arm (desquamation and erythema of nail fold, periungual irritation, paronychia).
Bianchi et al. (2003) [64]	Open, prospective	Topical tazarotene	Tazarotene 0.1% gel nonoccluded nightly	25 patients	22–66 years; 5 female patients and 20 male patients	Fingernails and toenails	At 12 weeks, 19/25 (76%) patients had reduction in onycholysis, hyperkeratosis, oil spots, and pitting (p < 0.0001). Initial improvements were noted in the fingernails after only 4 weeks of therapy. Hyperkeratosis and oil spots showed the most drastic and fastest improvement. Pitting was the most persistent sign. Moderate recurrences noted at 24 weeks post-therapy. The main recurrent sign was mild relapsing hyperkeratosis. Reported side effects included mild erythema (70%), proximal nail fold peeling (15%), burning (15%).
Diluvio et al. (2007) [65]	Case report	Topical tazarotene	Tazarotene 0.05% gel nonoccluded daily	1 patient	6/F	Fingernails	At 8 weeks, hyperkeratosis improved, fragility completely resolved, and nail growth was normal. Nail pitting persisted. No relapses were reported at follow-up. There was local skin irritation during the first week of treatment.
Fischer-Levancini et al. (2012) [66]	Open, prospective	Topical tazarotene	Tazarotene 0.1% ointment nightly	6 patients	Age NR; sex NR	NR	Mean nail psoriasis severity index was 14.3±6.3 at baseline. At 3 months, the average nail psoriasis severity index decreased to 8±3.29 (p = 0.007), and at 6 months, the average nail psoriasis severity index decreased to 2.3±1.21 (p = 0.003). At 6 months, complete resolution occurred for subungual hyperkeratosis in 5/6 (83.3%) of patients, splinter hemorrhages in 4/6 (66.7%), onycholysis in 3/6 (50.0%), pitting spots in 3/6 (50.0%), and oil spots in 2/6 (33.3%). Pain remission was observed in most cases. No adverse events were reported.
Piraccini et al. (2014) [67]	Case series	Topical tazarotene	Tazarotene 0.1% gel daily	2 patients	77/F; 38/M	Fingernails	Two patients with nail psoriasis developed pyogenic granulomas after treatment with topical tazarotene. Case 1: pyogenic granulomas observed after 3 months of tazarotene. Lesions were 0.5–1.5 cm in diameter and very painful. Tazarotene therapy was discontinued and after clobetasol propionate ointment twice daily for 2 weeks, the pyogenic granulomas regressed; case 2: pyogenic granuloma observed after 2 months of tazarotene. The lesion was 0.5 cm in diameter and mildly painful. The granuloma resolved after 4 weeks.
Tosti et al. (2009) [68]	Open, prospective	Oral acitretin	Oral acitretin 0.2–0.3 mg/kg daily	36 patients	Mean age 41 years; 9 female patients and 27 male patients	Fingernails	At 6 months, average fingernail psoriasis severity index score was reduced from baseline 31.5 to 18.6 (41% mean percent reduction, no p value reported). At 6 months, 9/36 (25%) had complete resolution, 9/36 (25%) had moderate improvement, 12/36 (33%) had mild improvement, and 11/36 (11%) had no improvement. One patient experienced adverse effects (severe dryness of periungual skin and multiple pyogenic granulomas 2 months after therapy).
López et al. (2009) [69]	Case report	Oral acitretin	25 mg daily	1 patient	60/M	Fingernails and toenails	Baseline physical exam was notable for oil drop discoloration, subungual hyperkeratosis, onycholysis, nail pitting, and paronychia. Clinical improvement after 2 months.
Ricceri et al. (2013) [70]	Case report	Oral acitretin	Oral acitretin 25 mg daily and 5% urea nail lacquer	1 patient	73/F	Fingernails and toenails	Baseline exam was notable for oil drop discoloration, subungual hyperkeratosis, nail pitting, paronychia, and onychogryphosis. Toenail involvement impeded the patient’s ability to walk. Clinical improvement was noted at 2 months of therapy, and improvement progressed 6 months later. Cheilitis was a reported side effect. The patient did not have relapse at 5 month follow-up.
Krajewska-Włodarczyk et al. (2021) [71]	Prospective, controlled observational	Oral acitretin	Oral acitretin 0.6–0.8 mg/kg daily	41 patients	Age 32–64 years; 24 female patients and 17 male patients	Fingernails	After 6 months of treatment, reduction of nail bed and matrix thickness was noted via ultrasound exam (p = 0.046, p = 0.031, respectively). Although thickness of nail plates decreased, this was statistically insignificant (p = 0.059). Modified nail psoriasis severity index decreased in over 80% of patients.
Graceffa et al. (2020) [72]	Case report	Oral acitretin and topical tacalcitol	Oral acitretin 10 mg twice daily and tacalcitol ointment once daily	1 patient	37/F	Fingernails and toenails	Paronychia remission with minimal improvement of nail dystrophy after 3 months. The patient was started on apremilast and clobetasol, which moderately improved nail dystrophy. Acitretin was decreased to 10 mg daily due to cheilitis, and apremilast was continued with the addition of tacalcitol ointment once daily. 2 months later, apremilast was discontinued due to nausea, and combination oral acitretin/tacalcitol ointment was continued. Between the baseline visit and 16-months, modified nail psoriasis score had decreased by 80% from 45 to 9; psoriasis area and severity index had declined from 3.2 to 0.6.
Brazzelli et al. (2004) [73]	Case report	Oral acitretin	Oral acitretin 0.5 mg/kg daily	1 patient	39/M	Fingernails and toenails	Complete clinical resolution after 6 months. There was no relapse at 5-month post-therapy follow-up, and the patient reported complete resolution of prior functional disability. Cheilitis and palmoplantar scaling were reported side effects.
Tosti et al. (2006) [74]	Case report	Oral acitretin	Oral acitretin 0.3 mg/kg daily	1 patient	38/M	20 fingernails and toenails	At 3 months, roughness, riding, subungual hyperkeratosis, and pitting had almost completely resolved. No side effects were reported. Therapy was discontinued after 7 months with complete resolution.
Tosti et al. (1998) [58]	Randomized, double-blind trial	Topical calcipotriol	Topical calcipotriol ointment 50 μg/g twice daily; betamethasone dipropionate (64 mg/g) and salicylic acid (0.03 g/g) ointment	58 patients	Mean age 51.8±14.8 years; 23 female patients and 35 male patients	Fingernails and toenails	After 3 months, fingernail subungual hyperkeratosis decreased by 26.5% in the calcipotriol group and 51.7% in the betamethasone group (p < 0.001 from baseline, no difference between groups). After 5 months, fingernail responders showed a 49.2% reduction in hyperkeratosis in the calcipotriol group and 51.7% in the betamethasone group (p < 0.001 from baseline, no difference between groups).
							After 3 months, toenail subungual hyperkeratosis decreased by 20.1% in the calcipotriol group and 22.9% in the betamethasone group (p < 0.001 from baseline, no difference between groups). After 5 months, toenail responders showed a 40.7% reduction in hyperkeratosis in the calcipotriol group and 51.9% in the betamethasone group (p < 0.0001 from baseline, no difference between groups). 3/4 patients underwent adverse events (erythema, periungual irritation, local burning sensation, and diffuse urticaria) in the calcipotriol arm.
Zakeri et al. (2005) [75]	Case series	Topical calcipotriol	Topical calcipotriol ointment 50 μg/g twice daily	24 patients	Mean age 33 years (18–68); 18 female patients and 5 male patients	Fingernails and toenails	At 3 months, 14/24 (58.3%) patients showed clinical improvement. At 5 months, 2/24 (8.3%) had complete resolution. Reduction in hyperkeratosis, onycholysis, and discoloration was especially notable. Fingernails had greater response than toenails. Two patients reported adverse effects (periungual irritation and pruritus/oozing). Most patients experienced recurrence of lesions with reduced severity after discontinuing calcipotriol.
Tzung et al. (2008) [76]	Randomized, investigator-blind, controlled trial	Topical calcipotriol	Topical 0.005% plus 0.05% betamethasone dipropionate ointment once daily; 0.005% calcipotriol ointment twice daily	40 patients	Mean age 53.2±19.1 years; 7 female patients and 25 male patients	Fingernails	At 12 weeks, total nail psoriasis severity index score had a statistically significant reduction in both treatment arms (p < 0.045). There was no difference between treatment arms using either investigator’s global assessment (p = 0.071) or nail psoriasis severity index (p = 0.649). No adverse events were reported.
Kole et al. (2014) [77]	Randomized, double-blinded trial	Topical calcitriol	Calcitriol ointment 3 μg/g twice daily; topical betamethasone dipropionate 64 μg/g twice daily	10 patients	Mean age 57 years (36–74); sex NR	Fingernails and toenails	At 20 weeks, average physician global assessment scale decreased from 2.5 at baseline to 1.25 in the calcitriol group, and 2.375 at baseline to 2.2 in the betamethasone group (p = 0.075 between groups). At 24 weeks, there was a 38 and 35% reduction in nail thickness in the calcitriol and betamethasone groups, respectively (p = 0.42 between groups).
Usmani and Wilson (2006) [78]	Case report	Topical calcitriol	Calcipotriol cream 50 μg/g twice daily, reduced to calcitriol ointment 3 μg/g after several days	1 patient	38/F	Fingernails	Improved new nail growth and resolved discoloration after 2 months. Further clinical improvement noted at 6 months. Recurrence occurred 3-months post-therapy with onycholysis, subungual hyperkeratosis, and nail pitting.
Márquez Balbás et al. (2009) [79]	Case series	Topical tacalcitol	Tacalcitol ointment 4 μg/g nightly	15 patients	Age NR; 7 female patients and 8 male patients	Fingernails	Clinical improvement observed at 3 months (p = 0.001, compared to baseline), 6 months (p = 0.001, compared to baseline), and at 6-months post-therapy (p = 0.004, compared to 3 months therapy). Greatest reduction in subungual hyperkeratosis and onycholysis, followed by oil drop discoloration and nail pitting. At 6 months, all 10 patients with baseline pain reported resolution of pain. No adverse events reported.